Liver and pancreas: 'Castor and Pollux' regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is found in 30-50% of diabetes mellitus (DM). Insulin resistance is triggering factor in both DM and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to investigate frequency of PEI in NAFLD, and relationship of fecal pancreatic elastase (PE) levels with liver histology and pancreatic fat. METHODS: Ninety-seven biopsy proven NAFLD patients and 50 controls were enrolled. Pancreas exocrine functions were measured by PE. Magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF) was used to quantify fat. RESULTS: NAFLD patients had significantly lower PE levels than controls (297 [204-517] vs. 500 [298-678] µg/g, p < 0.01). PEI (PE < 200 µg/g) ratio of NAFLD patients (22.7%, n = 22) was higher than PEI ratio of controls (6%, n = 3) (p = 0.011). Among diabetic (n = 35) NAFLD patients, 9 (25.7%) exhibited PEI, compared to 13 (21%) of non-diabetics. There was no significant difference in patients with and without DM in terms of PEI (p = 0.592). Among NASH (n = 68) patients 16 (23.5%) exhibited PEI, compared to (20.7%) of non-NASH (p = 0.76). Multiple analysis revealed NAFLD as a predictor of PEI independent of age, sex and DM (OR = 4.892, p = 0,021). Mean pancreas MRI-PDFF was significantly higher in diabetics (13.7% ± 3.6% vs. 8.7% ± 5.1%, p = 0.001). There was no significant pancreas MRI-PDFF difference between NASH and non-NASH (P = 0.95). Mean pancreas MRI-PDFF was significantly higher in patients with PEI (13.7% ± 3.4% vs. 8.9% ± 5.2%, P < 0.01). CONCLUSION: This is the first study demonstrating the high frequency of PEI in NAFLD independent of DM. Moreover, increasing pancreatic steatosis appears to be associated with higher frequency of PEI in NAFLD.

Value of Cystatin C-Based e-GFR Measurements to Predict Long-Term Tenofovir Nephrotoxicity in Patients With Hepatitis B.

BACKGROUND: Cystatin C is a genuine marker for detecting minor reductions in estimated glomerular filtration rate (e-GFR). STUDY QUESTION: We aimed to investigate the efficiency of cystatin C levels in predicting nephrotoxicity due to antiviral therapy in patients with chronic hepatitis B virus infection. STUDY DESIGN: Seventy-six naive hepatitis B virus patients and 44 controls were enrolled in this prospective cohort study. MEASURES AND OUTCOMES: Serum cystatin C, phosphate and creatinine levels, and urinary albumin/creatinine ratios of all patients were measured at baseline, 3rd, 12th, and 24th months. Nephrotoxicity was determined according to the amount of change in creatinine level at the fourth year of treatment compared with baseline ([INCREMENT]Cr0-4). RESULTS: Mean age was 36.1 ± 9.2 years and 40 (52.2%) of patients were women. There was no significant difference between baseline values of tenofovir disoproxil fumarate and entecavir groups. Although the creatinine level at the fourth year of treatment was statistically nonsignificant compared with baseline in the entecavir group, it was significantly higher in the fourth year of tenofovir treatment compared with baseline (0.95 ± 0.27 mg/dL vs. 0.76 ± 0.16 mg/dL, P = 0.002). While the increase in [INCREMENT]Cr0-4 was ≥0.2 mg/dL in 43.2% of patients in the tenofovir group, this rate was 18.8% in the entecavir group. Diagnostic accuracy in identifying decreased renal function as area under the curve (AUC) was high for baseline serum cystatin C level; furthermore, the highest AUC was calculated for cystatin C plus creatinine-based e-GFR equation (AUC: 0.81, P < 0.001). CONCLUSIONS: Long-term tenofovir disoproxil fumarate nephrotoxicity can be predicted by serum cystatin C plus creatinine-based e-GFR measured before treatment.

Role of Bismuth in the Eradication of Helicobacter pylori.

Bismuth salts exert their activity within the upper gastrointestinal tract through action of luminal bismuth. Bismuth exerts direct bactericidal effect on Helicobacter pylori by different ways: forms complexes in the bacterial wall and periplasmic space, inhibits different enzymes, ATP synthesis, and adherence of the bacteria to the gastric mucosa. Bismuth also helps ulcer healing by acting as a barrier to the aggressive factors and increasing mucosal protective factors such as prostaglandin, epidermal growth factor, and bicarbonate secretion. To date, no resistance to bismuth has been reported. Also synergism between bismuth salts and antibiotics was present. It was shown that metronidazole and clarithromycin resistant H. pylori strains become susceptible if they are administered together with bismuth. Bismuth-containing quadruple therapy was recommended both by the Second Asia-Pacific Consensus Guidelines and by the Maastricht IV/Florence Consensus Report as an alternative first choice regimen to standard triple therapy, in areas with low clarithromycin resistance, and it is recommended as the first-line therapeutic option in areas with a high prevalence of clarithromycin resistance. Greater than 90% eradication success can be obtained by bismuth-containing quadruple therapy. Choosing bismuth as an indispensable part of first-line therapy is logical as both metronidazole and clarithromycin resistances can be overcome by adding bismuth to the regimen.

First Week HCV RNA Level Under the Pegylated Interferon and Ribavirin Treatment Predicts Sustained Virological Response.

This study was planned to investigate whether the decrease in the hepatitis C virus (HCV) RNA levels at the first week of combined pegylated interferon and ribavirin treatment of naive genotype 1 patients with HCV was predicting sustained virologic response (SVR). Fifty-two patients were enrolled into the study. HCV RNA levels were measured at the baseline, first, fourth, and 12th weeks of treatment. Thirty-four patients achieved SVR, which basal, first week, and fourth week HCV RNA levels were log 5.57, log 3.65, and log 1.92, respectively. Eighteen patients could not achieve SVR, which basal, first week, and fourth week HCV RNA levels were log 6.22, log 5.45, and log 3.84, respectively (P < 0.05). Patients were distributed in 2 groups according to the amount of decrease in HCV RNA levels at the first week as less or more than 1.5 log. There were 20 patients with ≥1.5 log decrease in the HCV RNA levels at the first week. They were named as patients with very rapid virologic response (VRVR). All patients (100%) with VRVR were achieved SVR. In only 14 (44%) of the 32 patients without VRVR, SVR was achieved. In 16 (84%) of the 19 patients with rapid virologic response and 33 (79%) of the 42 patients with early virologic response, SVR was achieved. A ≥1.5 log decrease (VRVR) in HCV RNA levels of patients with HCV at the first week of combined pegylated interferon and ribavirin treatment predicts SVR very strongly.

Effect of Entecavir and Tenofovir Treatment on Noninvasive Fibrosis Scores: Which One Is Better?

Liver biopsy is the best method for detecting fibrosis grade of the liver in chronic hepatitis B. However, the invasiveness of liver biopsy complicates its routine use in follow-up of treatment. We planned to determine the usage of fibrosis predicting noninvasive scores in the follow-up of the treatment of patients with chronic hepatitis B treated with entecavir or tenofovir. Two hundred twenty-eight patients with hepatitis B with liver biopsy were included in the study. Fibrosis grade was determined by Ishak score. The laboratory data at months 0, 12, and 24 during treatment were collected and noninvasive fibrosis scores (aspartate aminotransferase to alanine aminotransferase ratio [AAR], aspartate aminotransferase to platelet ratio index [APRI], fibrosis index based on the 4 factors [FIB-4] and red cell distribution width to platelet ratio [RPR]) were calculated. Statistically significant increase in all scores and decrease in platelet count were observed as the fibrosis level increased. For differentiation of patients with fibrosis ≥grade 2, the highest sensitivity and specificity rates were shown by APRI score (sensitivity 67%, specificity 69%, and cutoff ≥0.5). FIB-4 was the most successful score for differentiation of patients with fibrosis ≥grade 3 (sensitivity 83%, specificity 74%, and cutoff ≥1.45). A significant decrease in all noninvasive fibrosis scores was observed at months 12 and 24 during treatment with both entecavir and tenofovir (P < 0.001). Among these, only the improvement in APRI score was found better in entecavir group with statistical significance (P < 0.05). APRI score was effective in demonstrating early-stage fibrosis. FIB-4, RPR, and platelet count were better in demonstrating advanced fibrosis. Although noninvasive scores cannot replace liver biopsy for diagnosis, they can be used for monitoring the response to treatment.

Insulin Resistance as a Novel Risk Factor for Post-ERCP Pancreatitis: A Pilot Study.

BACKGROUND AND AIMS: The relationship between insulin resistance and post-ERCP pancreatitis (PEP) is not known. We aimed to determine the relation between pre-ERCP insulin resistance and risk of PEP, and to evaluate the relationship of insulin resistance with well-established risk factors for PEP. METHODS: Consecutive patients who underwent ERCP with the diagnosis of choledocolithiasis between January and December 2013 were enrolled in this prospective study. Pre-procedural insulin resistance state and other risk factors were evaluated according to PEP development. RESULTS: Pancreatitis developed in 16 (11.3 %) of 141 ERCP procedure. Homeostasis model assessment of insulin resistance (HOMA-IR) levels was found statistically significantly higher in patients who developed PEP than the ones who did not (3.37 ± 0.8 vs. 2.38 ± 1.4, p < 0.001). Common bile duct (CBD) diameter of the patients developing PEP was found significantly lower than the non-PEP group (10.1 ± 4 vs. 13.4 ± 4.5 mm, p = 0.01). Mean procedure time was 33.5 min in PEP group and 27.9 min in non-PEP group (p = 0.006). HOMA-IR (OR 2.39), procedure time (OR 1.15), and CBD diameter (OR 0.82) were independent predictors of PEP development. CONCLUSIONS: The presence of insulin resistance is an important risk factor for PEP, and these data can be used as a considerable clue to predict the risk of PEP before ERCP and to decrease related morbidity.

Renal involvement in AA amyloidosis: clinical outcomes and survival.

BACKGROUND: The natural history of AA amyloidosis is typically progressive, leading to multiple organ failure and death. We analyzed the etiology as well as clinical and laboratory features of patients with biopsy-proven AA amyloidosis and evaluated the ultimate outcome. METHODS: Seventy-three patients (24 female; mean age 41.85±15.89 years) were analyzed retrospectively. Demographic, clinical and laboratory features were studied and the outcome was assessed. RESULTS: Familial Mediterranean Fever and tuberculosis were the most frequent causes of amyloidosis. Mean serum creatinine and proteinuria at diagnosis were 4.65±4.89 mg/dl and 8.04±6.09 g/day, respectively; and stage I, II, III, IV and V renal disease were present in 19.2%, 13.7%, 16.4%, 11%, and 39.7% of the patients, respectively. ESRD developed in 16 patients during the follow-up period. All of the ESRD patients started a dialysis programme. Thirty patients (41%) died during the follow-up period; median patient survival was 35.9±6.12 months. Old age, tuberculosis etiology, advanced renal disease and low serum albumin levels were associated with a worse prognosis. Serum albumin was a predictor of mortality in logistic regression analysis. CONCLUSION: The ultimate outcome of the patients with AA amyloidosis is poor, possibly due to the late referral to the nephrology clinics. Early referral may be helpful to improve prognosis.

Duodenal biopsy for diagnosis of renal involvement in amyloidosis.

Amyloidosis results from extracellular deposition of a fibrillary protein in various organs, and renal biopsy is the best, but a complicated tool for diagnosis. Therefore, alternative biopsy sites have been proposed with varying degrees of sensitivity. We aimed to find the most appropriate biopsy site in patients with chronic kidney disease (CKD) in whom renal biopsy is contraindicated or unavailable. 42 patients (29 male; mean age 46 ± 16 y) with CKD in whom amyloidosis was suspected as the underlying etiology on clinical grounds, but renal biopsy was not available (Group I), and 36 patients (25 male; mean age 40 ± 16 y) with CKD in whom renal biopsy revealed AA-amyloidosis (Group II) were investigated. Upper and lower gastrointestinal tract (GIT) endoscopies were performed and multiple biopsies from gingiva, esophagus, antrum, duodenum and rectum were obtained. In Group I, no amyloidosis was detected in gingival and GIT biopsies among 13 patients. In the remaining 29 patients AA-amyloidosis was detected in various sites with the following frequencies: duodenum 100%, rectum 83%, antrum 79%, esophagus 44% and gingiva 29%. In Group II, frequency of amyloid deposition was 97% in duodenum, 76% each in antrum and rectum, 59% in esophagus and 32% in gingival mucosa. In conclusion, duodenal biopsy is sensitive for diagnosing amyloidosis in CKD patients, and highly correlates with renal amyloidosis.

The Efficiency of Fractional Anisotropy, Apparent Diffusion Coefficient, and Contrast Enhancement Index in Liver Fibrosis Staging.

Objectives: Even though magnetic resonance imaging has been described as the most effective imaging method for the diagnosis of liver fibrosis, an accepted magnetic resonance imaging (MRI) technique is yet to be defined. The aim of this study is to determine the efficiency of MRI in the staging of liver fibrosis. Methods: Patients with chronic hepatitis B infection and had upper abdominal MRI with hepatocyte specific contrast agent were evaluated. Twenty-nine patients that had undergone liver biopsy were included in the study. ADC, FA, and signal intensity values of liver parenchyma were measured by two observers and contrast enhancement index (CEI) was calculated as well. Patients were grouped as early (A) and late fibrosis(B) according to Ishak grading system and then the correlations between the stage and MRI findings were analysed. The intraclass correlation coefficient was used to analyze the inter-rater agreements. ADC, FA, and CEI were compared with Student t-test between early and late fibrosis groups. Pearson's correlation was used to assess the correlation between ADC and FA values. Spearman correlation was used to evaluate the relationship between pathologic fibrosis grade and MRI parameters that were measured. Results: Twenty-two patients were staged as 1 and 2 (group A), seven patients were staged as 3 and above fibrosis(group B). Statistically, there was a strong, negative correlation between the FA values and the degree of fibrosis (r=-0.582, p=0.001). There was no correlation between the CEI and hepatocyte activity index (r=-0.88, p=0.655) and degree of fibrosis (r=0.0001, p=0.997). In terms of FA values, there was a statistically significant difference between two groups (group A=0.429 ± 0.06, group B=0.349 ± 0.06) (p=0.004). Conclusion: Correlation of FA values with fibrosis stage and significant difference in FA values between early-late stage fibrosis patients shows that diffusion tensor imaging can be a promising technique in the staging and follow-up of liver fibrosis.

The effect of sarcopenia and serum myokines on prognosis and survival in cirrhotic patients: a multicenter cross-sectional study.

OBJECTIVE: Sarcopenia is one of the most significant contributors to morbidity in patients with chronic liver disease. Serum myokines are potential biomarkers for detecting early sarcopenia. We aimed to investigate the relationship between serum myokines and cirrhosis-related mortality in the early stages of the disease. METHODS: In total, 262 patients and 50 healthy controls were enrolled in this study, which was designed as a multicenter cross-sectional study. At the beginning of the study, sarcopenia was defined by computed tomography scans using the third lumbar vertebra skeletal muscle index. Serum myostatin, irisin, and follistatin levels, nutritional status of the patients, and muscle strength as measured by the handgrip test were recorded. Cirrhosis-related mortality and overall survival were evaluated in the fourth year of the study as the second checkpoint of cross-sectional analysis. RESULTS: A total of 145 (55.3%) patients were diagnosed with sarcopenia. Multivariate analysis revealed that low BMI, high levels of myostatin, and decreased irisin levels were independent predictors of sarcopenia. While serum irisin level was the most predictive parameter in terms of 4th-year cirrhosis-related mortality in the CHILD A group, serum myostatin levels were found more indicative in the CHILD BC group regardless of sarcopenia status ( P < 0.001). CONCLUSION: Serum myostatin levels predict sarcopenia in all stages of cirrhosis. Serum irisin levels can also be used as a potential biomarker to predict both treatable sarcopenia and cirrhosis-related mortality in CHILD A patients.

Could complement C4 be an alternative to biopsy for chronic hepatitis B histopathologic findings?

BACKGROUND: Hepatitis B leads to chronic liver disease, cirrhosis, and hepatocellular cancer. Viral markers and other laboratory tests used in diagnosis and follow-up of chronic hepatitis B (CHB) do not correlate well with disease activity and liver histopathology. For this reason, alternative tests that indicate disease activity are needed. We aimed to investigate the utility of serum complement levels for follow-up in patients with CHB with normal and high transaminase levels. METHODS: One hundred forty-three patients that were evaluated between 2009 and 2010 were included in the study. Hepatitis B early antigen negative CHB cases with high transaminase levels were evaluated as the first group, and cases with normal transaminase level (inactive hepatitis B surface antigen carrier) as the second group, patients with cirrhosis were included as a third group. Age, sex, hepatitis B surface antigen, anti-HBcAg IgM, hepatitis B early antigen, anti-δ, anti-HCV, anti-HIV, serum hepatitis B virus (HBV) DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptidase (GGT), complement C3, and C4 levels of both groups were compared. The relationship between Knodell histologic activity index (HAI) score and fibrosis in liver biopsy specimens and serum complement levels of cases with high transaminase levels were investigated. FINDINGS: There were 49 patients with CHB with high transaminase levels; (Female/Male: 22/27). Mean age was 42.3±15.7 y, ALT=104.41±101.74, AST=69.7±65.2, GGT=35.37±20.4, C3 level=104.2±28.8, C4=16.11±4.17, and HBV DNA >2000 IU/mL (>105 copies/mL) in all cases. Remaining 27 patients had cirrhosis. There were 67 patients with CHB with normal transaminase levels (Female/Male: 32/35). Mean age was 39.56±12.9 y, ALT=22.7±5.5, AST=22±5.18, GGT=48.8±60.4, C3=117.85±22.15, and C4=21.44±5.46. Serum complement C4 level in 4 of the CHB cases with normal transaminase levels was low. Serum C3 (P=0.024) and C4 (P=0.001) levels in patients with CHB with high transaminase level were significantly lower. Low serum complement levels were negatively correlated with Knodell-HAI scores in patients with high transaminase levels (r=-0.84; P<0.001). There was no correlation between HAI and HBV DNA, AST, ALT, and GGT. There was no significant correlation between complement C3 and C4 levels and ALT, AST, HBV DNA, and GGT in any of the groups. Child score in patients with cirrhosis negatively correlated with both C3 (P=0.001) and C4 levels (P=0.001). Complement levels in patients with cirrhosis and CHB with high transaminase levels did not significantly differ. RESULTS: Serum complement C4 levels (in contrast to virologic markers and transaminases) significantly correlate with liver biopsy findings and may be a useful indicator of disease activity and/or damage in patients with CHB with high transaminase levels.

Serum fibrosis markers could aid in the prediction of factor for successful oral antiviral treatment in hepatitis C.

BACKGROUND: It has been demonstrated that there may be a relationship between liver fibrosis and serum biomarkers. The aim of this study was to investigate pre- and postoral antiviral therapy levels of these biomarkers and their relationship with other fibrotic parameters in hepatitis C virus (HCV) patients. METHODS: The study group comprised HCV patients who were treated with oral antiviral regimens. Prior to, and 8 months after the treatment, serum biomarkers, including transforming growth factor-ß (TGF-ß), chitinase-3-like protein 1 (YKL-40), collagen type IV, matrix metalloproteinases (MMPs) and hyaluronic acid levels, were examined and fibrosis-4 (Fib-4) and aspartate aminotransferase to platelet ratio index (APRI) scores were calculated at the same times. RESULTS: In total, 45 HCV patients (aged between 27 and 86 years) participated. Of these 20 (44.4%) were cirrhotic and 25 (55.6%) were noncirrhotic. The concentrations of YKL-40 (P = 0.01) and TGF-ß (P = 0.032) after treatment were significantly higher than the pretreatment values, whereas hyaluronic acid concentrations decreased after treatment (P = 0.001). Noncirrhotic patients had significantly higher (P = 0.03) YKL-40 levels prior to therapy compared to cirrhotic patients. Median MMP-2 concentrations were higher in men than in women (P = 0.001). Prior to treatment, TGF-ß, YKL-40 and collagen type IV levels were negatively correlated with Fib-4 scores, whereas only TGF-ß and YKL-40 concentrations were negatively correlated with APRI scores. CONCLUSION: YKL-40, TGF ß and hyaluronic acid may be markers for fibrotic change during oral therapy for HCV. In particular, TGF ß concentrations correlated with fibrotic indices. However, these results should be confirmed and validated by further research.

Characteristics of Newly Diagnosed Hepatocellular Carcinoma Patients Across Turkey: Prospective Multicenter Observational 3K Registry Study.

AIMS: To evaluate patient profile for epidemiological and clinicopathological characteristics and potential risk/prognostic factors in newly diagnosed hepatocellular carcinoma (HCC) patients across Turkey. METHODS: A total of 547 patients (mean (SD) age 62.6 (10.3) years, 81.9% were males) were included in this registry study. Data on patient characteristics, etiologies of HCC, laboratory values, and tumor characteristics and stages were recorded at study enrollment. RESULTS: HBV infection (68.2%) was the leading etiology, followed by HCV infection (17.2%), HDV infection (5.5%), alcohol (6.4%), and NAFLD (3.5%), as the major etiologies. Considering that 51.6% of the patients had >5 cm HCC, 44% were Child-Pugh B/C and 57% were BCLC B-D, it appears that a significant group of HCC patients were diagnosed at advanced stages. Of 540 patients, 271 (50.2%) were referred or applied with the diagnosis of HCC. Patients with HCC at presentation had larger tumor size (median (min-max) 6.6 (0-30) vs. 4.8 (0-90) cm, P < .001) and more advanced BCLC stage (Stage C-D in 40.8% vs. 26.4%, respectively, P = .005), compared to patients who were diagnosed during follow-up. CONCLUSIONS: Our findings revealed that HBV infection was the leading etiology and a moderate-to-advanced disease was evident in more than half of patients at the time of diagnosis. HCC patients diagnosed at follow-up had smaller tumor size and earlier BCLC stage.

Factors predicting outcome of balloon dilatation in achalasia.

BACKGROUND: Balloon dilatation of the lower esophageal sphincter (LES) is one of the effective nonsurgical treatment options in the management of achalasia. We aimed to determine the long-term results of graded balloon dilatation and the factors predicting outcome. PATIENTS: Patients followed for more than 12 months between January 1995 to March 2005, without history of endoscopic or surgical therapy before the study, were included (n = 111, mean age 46.3 +/- 16.9 years; follow-up period 46.3 [12-150] months). Patients were evaluated by barium swallow contrast studies, upper endoscopy, and esophageal manometry. Pneumatic dilatation was performed with the use of polyethylene balloon system. Patient outcome was evaluated according to manometric studies and Van Trappen staging as determined following face-to-face interviews with the patients. RESULTS: We determined clinical response rates of 98%, 85.7%, and 75% at months 24, 48, and 60. According to receiver-operating characteristics (ROC) analysis, age or=30.5 mmHg, LESP after first balloon dilatation >or=17.5 mmHg, and balloon number >2 were found to negatively affect treatment response. Young age and higher esophageal body pressure at admission were determined to be negative predictive factors (P = 0.038, relative risk (RR) 2.6, 95% confidence interval [CI] 1.05-6.4 and P = 0.05, RR 1.069, 95% CI 0.99-1.14, respectively). CONCLUSION: Balloon dilatation is an effective treatment of achalasia. Young age, higher esophageal body pressure, and high LESP after first balloon dilatation are negative predictive factors. Patients with young age requiring more than two balloon dilatations are likely to be unresponsive to the treatment.

Expression of p53, VEGF, microvessel density, and cyclin-D1 in noncancerous tissue of inflammatory bowel disease.

We aimed to evaluate the carcinogenesis risk in inflammatory bowel disease via p53 mutation and its relation with hyperproliferation (cyclin-D1) and angiogenesis (with vascular endothelial growth factor [VEGF] and microvessel density) and whether these events play important roles in pathogenesis of inflammatory bowel disease. Colonic tissue samples of 26 ulcerative colitis, 6 Crohn's disease, and 8 amoebic colitis patients as well as samples of 10 healthy controls were stained with p53, cyclin-D1, CD34, and VEGF monoclonal antibodies by immunohistochemistry and evaluated semiquantitatively. Expression of p53 was higher in ulcerative colitis than in the healthy control and amoebic colitis groups (4.15 +/- 2.07, 1.4 +/- 1.5, 1.3 +/- 1.5; P < 0.001). The Crohn's disease group had the highest p53 expression (4.6 +/- 1.6). The Crohn's disease, ulcerative colitis, and amoebic colitis groups all had higher VEGF expression than did the healthy controls (respectively, 4.3 +/- 1.2, 2.92 +/- 2.0, 2.3 +/- 1.5, 0.6 +/- 0.97; P < 0.001). Also, microvessel density was statistically higher in all three colitis groups than in healthy controls. Cyclin-D1 expression in all four groups was similar. The study showed that p53 mutation was present in nonneoplastic mucosa of inflammatory bowel disease patients. Detecting strong p53 overexpression with VEGF overexpression may help in differentiating inflammatory bowel disease from other colitis.

Changes in Liver Tissue Trace Element Concentrations During Hepatitis B Viral Infection Treatment.

Approximately 350-400 million people in the world have Hbs Ag (hepatitis B virus surface antigen) positivity. In the international guidelines, the permanent suppression of replication in chronic hepatitis B virus (HBV) infection therapy is reported as the primary therapeutic goal. Trace elements play a key role in liver diseases. The aim of our study is to determine some trace element concentrations in the liver during HBV treatment periods. The measurement of 11 trace elements (manganese, lead, nickel, chromium, cadmium, iron, copper, zinc, silver, cobalt, and aluminum) was carried out by the method of inductively coupled plasma mass spectrometry in liver biopsy materials (before starting treatment and at the sixth month of the treatment period). There was an increase in zinc and copper concentrations in liver materials at the sixth month of treatment compared to the pre-treatment values (the median zinc value was 48.05 µg/g before treatment and 74.9 µg/g at 6 months after initial treatment, p = 0.035; median copper was 2.82 µg/g before treatment and 5.31 µg/g after 6 months, p = 0.002). General estimations indicated that zinc (p = 0.002), iron (p = 0.0244), copper (p = 0.0003), and aluminum (p = 0.0239) values may be effective in HAI (histological activity index) changes. Only iron levels could be at a very low level effective on the changes caused by fibrosis (p = 0.0002). Liver tissue zinc and copper levels increased in parallel with the improvement of inflammation in antiviral-treated HBV patients. In addition, the levels of zinc and copper in the liver tissue can be useful markers for liver tissue damage detection.

Sarcoidosis with Hepatic Involvement: A Case Report.

Sarcoidosis is a systemic, noncaseating granulomatous disease with an unknown etiology. The liver is one of the most frequently affected organs. This case is presented to emphasize that hepatic granulomatous foci can lead to a determination of etiology in a diagnosis of sarcoidosis. A 53-year-old-female patient with complaints of fatigue and abdominal pain was admitted to the clinic of gastroenterology. The blood levels of alanine transaminase, aspartate transaminase, alkaline phosphatase and gamma-glutamyl transferase were markedly increased. The autoimmune parameters were negative. A Tru-Cut biopsy (Becton, Dickinson and Co., Franklin Lakes, NJ, USA) of the liver was performed based on the initial diagnoses of tuberculosis, lymphoma, and sarcoidosis. Histopathological evaluation revealed noncaseating granulomatous inflammation with Grade 3 macrovesicular steatosis. An investigation for hepatic sarcoidosis was recommended. The angiotensin-converting enzyme levels were 5 times higher than normal. Based on this result, the diagnosis was sarcoidosis with hepatic involvement. The treatment and follow-up of the patient continues.

Management of iatrogenic injuries due to endoscopic sphincterotomy: Surgical or conservative approaches.

OBJECTIVE: The best therapeutic approach for endoscopic retrograde cholangiopancreatography-related perforations remains controversial; while some authors suggest routine conservative management, others advocate mandatory surgical exploration. We aimed to evaluate our clinical experience of perforations during endoscopic sphincterotomy. MATERIAL AND METHODS: A retrospective chart review from January 2010 to October 2015 identified 20 patients with endoscopic retrograde cholangiopancreatography-related perforations. Data collection included demographics, time to diagnosis, type of perforation, treatment strategy, surgical procedure, complications, hospital stay, and outcome. All patients were classified into two groups on the basis of radiological and operative findings. RESULTS: Only five patients underwent surgical treatment, whereas 15 patients were managed conservatively. The mean time to diagnosis was 7.8 hrs (range: 1 to 36 hrs). In patients who underwent surgical treatment, the types of perforations included type I and III in one patient each and type II in three patients. Surgical procedures included laparoscopic and open cholecystectomy with t-tube drainage in two patients each and primary repair of duodenal injury with hepaticojejunostomy in one patient. Among conservatively managed patients, eight, four, and three had type II, type III, and type IV injuries, respectively. Of these 15 patients, 60% (n=9) underwent percutaneous procedures. The mean length of hospital stay was similar for conservatively and surgically treated patients (12 vs. 12.4 days, respectively, p=0.790). One patient (5%) with type I injury died of multiorgan deficiency. CONCLUSION: With close close clinical follow-up, medical treatment can be beneficial for most patients, and surgical procedures should be reserved for patients with type I (definite) and type II/III injuries; in patients with these clinical parameters, conservative management will likely be unsuccessful.

Distribution of gastric lymphoid follicles in Helicobacter pylori-associated gastritis.

BACKGROUND/AIMS: Lymphoid follicles and the satellite lesions (intestinal metaplasia, atrophy and dysplasia) are known as precursor lesions of mucosa associated lymphoid tissue lymphomas in gastritis. Little is known about their prevalence in different distributions and types of Helicobacter pylori-associated gastritis. The aim of the study was to estimate the topographic prevalence of these lesions in gastritis related with Helicobacter pylori and to associate them with the density of bacteria. METHODOLOGY: Histology for the type of gastritis and for lymphoid follicles and Helicobacter pylori density were studied in antrum and/or corpus biopsies taken from 107 consecutive patients with clinical diagnosis of peptic ulcer. RESULTS: Lymphoid follicles, panmucosal and superficial gastritis were seen in 31 (31.9%), 84 (86.6%) and 13 (13.4%) out of 97 antrum biopsies, respectively. In the corresponding 28 corpus biopsies, these lesions were seen in 8 (28%), 15 (54%), 13 (46%), respectively. Lymphoid follicles were found more in panmucosal than superficial gastritis in the antrum, however in the same ratios in the corpus. In association with lymphoid follicles, Helicobacterpylori was positive in 7 (87%) of 8 corpus biopsies and in all (100%) of 31 antrum biopsies. No relation was observed between lymphoid follicles and Helicobacter pylori density. CONCLUSIONS: Examination of antrum biopsies rather than corpus biopsies would be sufficient to screen precarcinogenic lymphoid follicles in Helicobacterpylori associated gastritis.

Etiopathogenesis, Prevention, and Treatment of Thromboembolism in Inflammatory Bowel Disease.

The close relationship between inflammation and thrombosis affects the progression and severity of inflammatory bowel disease (IBD). The prevalence of venous thromboembolism (VTE) varies between 1% and 7% among patients with IBD. The VTE risk in patients with IBD is at least 3 times higher than that in the normal general population. The absolute risk is very high during hospitalization, active disease, and surgery. The IBD-related VTE occurs at younger ages and recurs more frequently. The development of thrombosis in IBD is due to the interaction of many hereditary and acquired risk factors. Each patient diagnosed with IBD should be evaluated for a personal and family history of thrombosis and for prothrombotic drug use. Although procoagulant factors are increased during the natural course of inflammation, natural anticoagulants and fibrinolytic activity are decreased. Although IBD is accepted as a prothrombotic condition, there is no treatment that can remove this risk from daily practice. Patient training is required to control important factors, such as long-term immobilization and smoking. Oral contraceptives and hormone replacement therapy should be avoided. Inducing permanent disease remission must be the key approach for the prevention of thrombosis. Low-molecular-weight heparin (LMWH) is the basis of prophylactic treatment, which reduces the thrombosis risk by 50%. Prophylaxis with LMWH should be administered to all patients with IBD hospitalized due to disease attack or surgery. Long-term or even life-long anticoagulation therapy should be planned if there is insufficient disease control, recurrent VTE attacks, positive thrombophilia tests, or thrombosis in vital veins.